The major objective of this research proposal is to study radiation-induced thyroid cancer by a coordinated program of clinical and basic endocrinological investigations. The clinical studies are designed to determine the current risk and continuing incidence of radiation-induced thyroid cancer and to evaluate methods of diagnosis and medical and surgical approaches to treatment. This will be accomplished by a longitudinal study of patients who have been evaluated at Michael Reese Hospital because of a history of childhood head or neck irradiation. Of 5,200 patients who were so treated, 1,500 already have been examined and another 1,000 have been contacted by mail. Among those examined, a 31 percent prevalence of nodules was found, and among those who had surgery, a 32 percent rate of carcinoma was determined. Follow-up examinations of these patients will provide the information necessary to develop clinical guidelines for the care of persons with a history of head or neck irradiation. Laboratory studies will focus on the role of plasma thyroglobulin in the diagnosis of thyroid tumors. Preliminary data sowed that plasma thyroglobulin was elevated in many patients with thyroid nodules but that it was not suitable as a single screening procedure. Detailed studies of the molecular properties of plasma thryoglobulin will be undertaken in order to improve its diagnostic usefulness and to understand how it enters the circulation. In addition, an in vitro system will be used to determine at what point thyroglobulin is released from the thyroid into the circulation. The early events in radiation-induced thyroid cancer formation will be studied by irradiating rat thyroid glands. The immediate and long term effects of radiation in causing hormonal changes and tissue damage will be determined by sequential measurements of thyroglobulin, TSH and thyroxine. These effects will be correlated to the number of cancers formed, so that their role in thyroid cancer induction can be evaluated. The ability of thyroxine suppressive therapy to prevent cancer formation also will be tested in this system.